Schizophrenia Research 115 (2009) 278285

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Schizophrenia Research
j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / s c h r e s

Theory of mind impairment in patients affected by schizophrenia and in

their parents
S. Anselmetti a,d,, M. Bechi a,d, M. Bosia b, C. Quarticelli b, E. Ermoli a,
E. Smeraldi a,b,c,d, R. Cavallaro a,b,d
a
b
c
d

Department of Clinical Neurosciences, San Raffaele Universitary Scientic Institute Hospital, Via Stamira d'Ancona 20, 20127 Milano, Italy
Vita-Salute San Raffaele University, Milan, Italy
National Institute of Neuroscience, Italy
Division of Neuroscience, San Raffaele Universitary Scientic Institute Hospital, Via Stamira d'Ancona 20, 20127 Milano, Italy

a r t i c l e

i n f o

Article history:
Received 23 July 2009
Received in revised form 9 September 2009
Accepted 16 September 2009
Available online 8 October 2009
Keywords:
Schizophrenia
Theory of mind
Parents
Cognitive functioning

a b s t r a c t
Theory of mind (ToM) is the ability to judge the mental states of the self and others. It is
currently considered as a part of the broader concept of social cognition, known to inuence the
social behaviour of patients affected by schizophrenia. Recently it has been hypothesized that
the impairment of ToM is a trait that can be detected both in patients with schizophrenia and in
non-psychotic relatives of patients, but it still not clear what the contribution of the familial
patterns of cognitive impairment is.
The aim of this study is to assess parental impairments of ToM performance considering the
effects of the neurocognitive abilities known to be impaired in their rst-degree relatives and to
inuence ToM in schizophrenic patients.
Patients, their parents and control trios were assessed with the Wisconsin Card Sorting Test
(WCST), the Symbol Coding Task and the ToM Picture Sequencing Task. The ANCOVA analysis
on 47 trios including a schizophrenic offspring and 47 healthy trios showed a statistically
signicant poorer performance of patients and their parents in comparison to control trios at
Symbol Coding Task and ToM task. Moreover a regression analysis showed that the
neuropsychological abilities tested were signicant predictors of ToM performance only in
patients. Results conrm a ToM impairment among parents of patients with schizophrenia that
is not directly correlated to other aspects of neurocognitive functioning.
2009 Elsevier B.V. All rights reserved.

1. Introduction
Difculties in several skills regarding domains of social
functioning, such as communication, interpersonal relationships, family and occupational roles are typical in patients with
schizophrenia (Priebe, 2007). Theoretical models have been
elaborated relying on a cognitive perspective that distinguishes

Corresponding author. Department of Clinical Neuroscience, San Raffaele

Universitary Scientic Institute Hospital, Vita-Salute San Raffaele University, Via
Stamira d'Ancona 20, 20127 Milano, Italy. Tel.: +39 0226433218; fax: +39
0226433265.
E-mail address: anselmetti.simona@hsr.it (S. Anselmetti).
0920-9964/$ see front matter 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.schres.2009.09.018

between social cognition a domain of cognition that

involves the perception, interpretation, and processing of social
information (Adolphs, 1999), social competence assessed in
laboratory context and social behaviour in the real-world
(Bellack et al., 1994). Global neuropsychological efciency was
shown to be signicantly related to performance in many realworld functional domains including social behaviour, with
signicant relationships between specic cognitive and functional domains (Green et al., 2000; Bowie and Harvey, 2008).
Recently, Bowie and Harvey (2008) showed that cognitive
abilities are relevant both for the acquisition of social or living
skills and for the deployment of these skills in the real-world. In
that study, effects of cognitive performance were signicantly
related, both directly and indirectly, to social behaviour

S. Anselmetti et al. / Schizophrenia Research 115 (2009) 278285

components. Among these, interpersonal behaviour was

directly predicted by processing speed and executive functions,
and indirectly predicted by attention and working memory
capacities through the mediating effect of social competence.
These last ndings supported the hypothesis that performance
underlying social cognition might be a mediator between
neurocognitive functioning and social outcomes in the realworld (Green et al., 2000).
Given their role in the development of correct social
cognition skills, it is noticeable that most of the above cited
neuropsychological abilities involved in social cognition were
also consistently impaired in unaffected rst-degree relatives.
Familial studies regarding neuropsychological performance
found a signicant impairment in rst-degree relatives'
performance, affecting the majority of cognitive domains
(Roxborough et al., 1993; Laurent et al, 2002; Keefe et al.,
1994, for a meta-analysis, Snitz et al., 2006). In some studies the
degree of impairment in the unaffected relatives was shown to
be intermediate compared to patients and healthy controls
(Kremen et al., 1994; Keefe et al., 1994; Egan et al., 2001).
However, results of single studies are still contradictory,
probably because they differ both in the degree of relatives
included (sibling, parents or offspring) and in the tasks
assessed. Most studies included unspecied rst-degree
relatives (mainly siblings and parents) and showed an
impairment on the part of rst-degree relatives in sustained
attention (Kremen et al., 1994; Chen et al., 1998), verbal and
working memory (Conklin et al., 2000, 2005), verbal uency
(Laurent et al., 2002) and executive function (Krabbendam
et al., 2001; Toulopoulou et al., 2003). More recently Bove
(2008) conrmed that relatives presented only a slightly
worse cognitive performance than controls, manifesting
lower scores especially in the tasks requiring a greater
cognitive processing load. Some other studies included only
siblings, in order to reduce the confounding effect of age and
found an impairment in non-affected siblings in all measures
of functioning, especially verbal memory, abstraction and
attention (Franke et al., 1994; Cannon et al., 1994), cognitive
exibility (Egan et al., 2001) and verbal uency (Hughes
et al., 2005). Niendam et al. (2003) reported that children
who later developed schizophrenia and their siblings
showed similar patterns of decits involving spatial reasoning, verbal knowledge, perceptual-motor speed and working
memory.
Few studies focused specically on parents of patients
with schizophrenia. In a review Docherty (1994) provided
substantial evidence that non-affected parents of patients
with schizophrenia show subtle cognitive difculties in the
area of concept formation and maintenance. Harris et al.
(1996) demonstrated that neuropsychological dysfunctions
in attention and learning were found only in a subgroup of
parents of patients with a family history of schizophrenia.
Dollfus et al. (2002) found a signicant impairment in parents
of patients with schizophrenia in a verbal uency task. In
Appels et al. (2003) study, parents of schizophrenic patients
were more impaired than healthy control couples on global
verbal memory, motor skills, sustained attention and verbal
uency.
Nevertheless, social behaviour itself involves the integration of different skills such as Theory of mind, perception
of social signs, recognition of facial expressions, attention,

279

memory, decision making processes and motivation. Most of

these components of social cognition were found to be
impaired in patients with schizophrenia, in particular Theory
of mind (ToM) (Frith and Corcoran, 1996), the ability to
judge the mental states of the self and others.
Impairments in the performance of a number of social
cognition and social competence tests have been suggested
in the literature also in relatives of patients with schizophrenia (Toomey et al., 1999; Mirsky et al., 1992), but no
studies have evaluated their inuence on social behaviour
in the real life. Toomey et al. (1999) found that relatives of
patients with schizophrenia were decient in the social
perception of non-verbal cues when compared to healthy
controls. First-degree relatives showed memory impairment
in recognition of faces (Conklin et al., 2002) and in visual
scan paths of emotional faces (Loughland et al., 2004). Previous research demonstrates that relatives display measurable decits also in pragmatic aspects of expressive language
(Mazza et al., 2008) as well as in their ability to verbalize
emotions (Marjoram et al., 2006). Other studies have used
the Eyes Test (Baron-Cohen et al., 2001) designed to measure
affective ToM with inconsistent results: Irani et al. (2006)
found that relatives of patients with schizophrenia showed
an intermediate performance between patients and healthy
controls, while Kelemen et al. (2004) did not nd any differences on the Eyes Test measure between relatives of patients
with schizophrenia and healthy controls. Janssen et al. (2003)
showed a signicant relatednessresponse relationship in the
association between schizophrenia and errors on the Hinting
Task, specically assessing the Theory of mind (Corcoran et al.,
1995), with patients having the highest probability of bad
performance, and rst-degree relatives having intermediate
values.
On the other hand, some issues regarding the signicance
and the nature of these last results on rst-degree relatives
regarding social cognition and theory of the mind in particular have not been sufciently addressed yet.
The rst point is that while for patients impaired performance on testing is related to failures in social cognition
performance in real life (Brune, 2005; Bora et al., 2006) the
same kind of failure has not been studied among their
unaffected relatives, who in most cases are within the normal
range.
Second, the ndings that neuropsychological performance
may be an intermediate phenotype limits the interpretation
of social cognition data in that cognitive impairments
are correlated with social cognition performance (at least in
the laboratory) in patients with schizophrenia. Subsequently,
the impairments in social cognition might also be inuenced
by neuropsychological performance impairments for parents,
possibly inuencing the abilities tested. In fact, it is still a
matter of debate if performance on ToM tasks is an independent function or whether it reects a dysfunction of other
cognitive abilities such as attention, memory and general
intelligence. Some authors argued that the ToM decits in
schizophrenia are part of a generalized intellectual decline
(Brune, 2003), but there is evidence that decits in the Theory
of mind in schizophrenia cannot be explained by the effect
of lower IQ alone (Mazza et al., 2001). However, recent
studies found that ToM performance impairment was related
to executive functions (Brune, 2005), verbal memory (Greig

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S. Anselmetti et al. / Schizophrenia Research 115 (2009) 278285

et al., 2004), and attentional (Randall et al., 2003) performance in patients with schizophrenia.
The presence of neuropsychological impairment could
then rather be a confounding factor in the analysis of social
cognition impairments among both patients and their
relatives, particularly for ToM. With the available data, two
major hypotheses could explain ndings of impairment of
ToM in patients with schizophrenia and their relatives. One is
to assume that impairment at this level is related to the wellknown familial neuropsychological decits (Janssen et al.,
2003). This hypothesis implies that if the effects of neuropsychological performance are controlled statistically the
differences in ToM tasks between patients with schizophrenia
and healthy controls would diminish; this effect could be
even stronger among relatives, since they show an intermediate degree of impairment between their ill relatives and
healthy controls. Alternatively, impairment in ToM among
patients with schizophrenia and their relatives may be
hypothesized as a distinct trait, generally independent from
neuropsychological functioning (Frith and Corcoran, 1996).
Even if ToM appears to be an innate potential ability
in humans (Baron-Cohen, 1989; Baron-Cohen et al., 1999), it
nevertheless requires some social experiences over many
years for it to be successfully developed (Ruffman et al.,
2002). It has been proposed that the parentchild social
interactions, especially for mothers, have important roles in
children's social cognitive development, with studies on
healthy subjects showing that maternal high mind-mindedness (the tendency to focus on the mind of infants) and
mother's use of appropriate mental state comments in
the rst year of life contributed to future mental abilities of
the child (Dunn, 1991; Ruffman et al., 2002; Meins et al.,
2002, 2003). For this reason, studying parents might have the
advantage of focusing on the relatives with the greatest
developmental potential impact on the future patients
(Docherty, 1994).
Determining whether ToM impairment is independent
from cognitive functioning in parents of patients with
schizophrenia could be a further step in the development of
a better hypothesis of the development of social cognition
impairment in schizophrenia.

psychotic disorder. Detailed family history of the parents was

collected up to the 2nd degree relatives of the parents. Other
exclusion criteria were a history of recent (one year) substance dependence or abuse, a comorbid diagnosis on Axis II,
epilepsy or any other major neurological illness or perinatal
trauma. All patients had to be treated with a stable dose of
the same antipsychotic monotherapy for at least 6 months
and to be a responder (good response was dened as a reduction of 30% or more in PANSS Total Score after 3 months of
treatment).
Forty-seven control families were recruited from hospital
staff and the general population and were screened for psychiatric diagnosis and family history with a clinical interview.
As well as for the patient trios, history of neurological illness
resulted in the exclusion, as did a history of psychotic disorders and substance abuse. Written informed consent was
obtained from all subjects after full explanation of the study
aims and procedures. Study protocol and procedures were
approved by the local Ethical Committee (ASL Citt di Milano
n 318/06).
3.2. Assessments
Patients were assessed for psychopathology, neurocognitive
performance and ToM performance. Healthy control families
and parents of patients with schizophrenia were assessed for
neurocognitive performance and ToM performance. Basic information such as age, sex, education, duration of illness and
medication were collected. A familiar history of psychosis since
second-degree relatives was also collected in families of parents
of patients with schizophrenia.
Twenty-nine families did not show any history of
psychosis, 2 families showed a familiar history of psychosis
in both members of the couple and 7 mothers and 9 fathers
showed a familiar history of psychosis.
3.2.1. Psychopathology
Psychopathology was assessed by means of the Positive and
Negative Syndrome Scale (PANSS) (Kay et al., 1989), administered by a trained psychiatrist.

3.1. Participants

3.2.2. Premorbid Intelligence

Premorbid Intelligence was assessed in all subjects using
the Test di Intelligenza Breve (TIB) (Sartori et al., 1997) the
Italian adaptation of the New Adult Reading Test (Nelson,
1982). The TIB consists of 54 words (34 effective test-words
with irregular accent and 20 control-words with high frequency of use), and requires the subjects to read out a list of
Italian words with a dominant (regular) and a less frequent
(irregular) stress pattern. The total number of reading mistakes denes the TIB error score. The estimated IQ scores
(ie, performance, verbal and total) are calculated through the
regression of equations taking into account sex, age and
educational level.

Forty-seven patients with DSM-IV (APA, 1994) chronic

schizophrenia and their parents were recruited from the
Department of Clinical Neurosciences, San Raffaele Hospital,
Milan. Trios were screened for Axis one psychiatric diagnosis
with a clinical interview (SCID I) and excluded if at least one
of the parents satised the diagnosis of schizophrenia or any

3.2.3. Neuropsychological functioning

Among the many possible cognitive functions known to
be impaired in patients with schizophrenia, we tested the
two most common variables reported in the literature to
be correlated with ToM abilities and to be impaired also in
relatives of patients: cognitive exibility and attention, as

2. Aim of the study

This research aimed to study the ToM performance among
patients with schizophrenia and their parents, taking into
account the effect of the most important neurocognitive
abilities known to inuence ToM's performance and to be
impaired in the rst-degree relatives of schizophrenic
subjects.
3. Materials and methods

S. Anselmetti et al. / Schizophrenia Research 115 (2009) 278285

previously mentioned (Brune, 2005; Greig et al., 2004;

Randall et al., 2003). All subjects received a neuropsychological battery including: computerized Wisconsin Card
Sorting Test (WCST; Stratta et al., 1997) for the evaluation
of cognitive exibility, and the Symbol Coding from the
Brief Assessment of Cognition in Schizophrenia (BACS; Keefe
et al., 2004), adjusted for age and education (Anselmetti
et al., 2008), for the evaluation of attention. Outcomes of
interest were the number of perseverative errors for WCST
and the number of correct answers for the Symbol Coding
Task.
3.2.4. Theory of mind
ToM was assessed using the Theory of Mind Picture
Sequencing Task (Brune, 2005), consisting in six cartoon
picture stories (Brune, 2003) of four cards each. There were
three types of stories depicting (1) a scenario where two
characters cooperated; (2) a scenario where one character
deceived a second character; and (3) a scenario showing
two characters cooperating to deceive a third. The cards
were presented face-down in mixed order. The participants were asked to turn the cards over and to order them
in a logical sequence of events. The sequencing time was
measured for each picture story. In addition, a ToM questionnaire with 23 questions was given to the subjects to
test their ability to appreciate the mental states of the
characters involved in the cartoon stories. The questions
referred to the mental states of the characters of the picture
stories according to different levels of complexity. Among
ToM questions, a set of Reality Questions, involving only
the general ability of physical information processing
rather than ToM was included as control items. Outcomes
consisted of the Sequencing Reaction Time, the Sequencing
Total Score and the number of correct answer in the
Questionnaire.
The main outcome variable of interest of this study was
the Total Score of sequencing and questionnaire subscales (59
points maximum) calculated as a global performance index as
previously described (Brune, 2005).
Neuropsychological and metacognitive tasks were administered by a trained psychologist.
3.3. Statistical analyses
Analysis of variance (ANOVA) was rst performed on
clinical and epidemiological data, including TIB. Analyses of
covariance (ANCOVA) were performed to test group effects
on neuropsychological variables, considering the variables
found signicantly different between groups in the exploratory ANOVA as covariates. The analysis was performed
separately in patients vs. controls and parents of patients vs.
parents of controls. In the analysis of neuropsychological
functioning covariates were age, education and TIB, when
relevant. In the analysis of ToM variables, covariates were age,
education, TIB and neuropsychological functioning, when
relevant. Post-hoc analysis was performed with the Tukey
Test.
A multiple regression analysis was used to model if ToM
performance of patients and their parents could be predicted
by cognitive functioning. Corrections for multiple comparison
were performed with Bonferroni test, when appropriate.

281

4. Results
Table 1 shows demographic variables of the sample and
ANOVA results. Regarding pharmacological treatment, 25
patients were treated with clozapine (median dose 250 mg),
13 patients with risperidone (median dose 4 mg), 5 patients
with aripiprazole (median dose 15 mg) and 4 patients with
haloperidol (median dose 4 mg). Patients and controls were
matched for age but they differed for education (F = 16.7
p < .001) and TIB score (F = 40.54 p < .001). Parents of patients
and healthy controls differed for both age (F = 8.05 p = .005 for
mothers and F = 14.25 p < .001 for fathers) and education
(F = 11.31 p = .001 for mothers and F = 6.61 p = .01 for fathers)
but not for TIB score.
4.1. Neuropsychological performance
A rst ANOVA analysis assessed possible sex (patients and
control groups) and medication (patients only) differences
on neuropsychological performances, showing no signicant
results.
Table 2 shows neuropsychological and ToM performance
of the sample and ANOVA results.
4.1.1. Patients vs. controls
The ANCOVA for the WCST showed a signicant group
effect (F = 19 p < .001) and a covariate effect for TIB (F = 6.08
p = .02). The ANCOVA for Symbol Coding Task (F = 59.01
p < .001) showed a signicant group effect, with no signicant covariate effect.
4.1.2. Parents of patients vs. parents of controls
The ANCOVA for Symbol Coding Task showed a signicant
group effect (F = 3.8 p = .01) and a signicant covariate effect
for education (F = 32.46 p = .000) and age (F = 11.56 p < .001).
Post-hoc analysis showed signicantly worse performance on
the part of the patients' mothers compared to controls' mothers
(p < .001) and patient's fathers compared to controls' fathers
(p < .001). The ANCOVA for WCST showed no group effect.
No differences were found in neuropsychological performance within parents of patients with schizophrenia regarding
the presence/absence of a family history of psychosis among
the parents' ancestors.
4.2. ToM Picture Sequencing Task
A rst ANOVA analysis assessed possible sex and medication differences related to ToM skills in patients group. No
signicant differences resulted either for sex or for medication for any of the variables considered.
4.2.1. Patients vs. controls
ANCOVA for the Total Score showed a signicant group
effect (F = 15.2 p < .001) and a covariate effect for the WCST
(F = 5.99 p = .01), Symbol Coding Task (F = 4.87 p = .03) and
TIB score (F = 8.97 p = .004). The ANCOVA for Reaction Time
Score showed a signicant group effect (F = 10.42 p = .002)
without any signicant covariate effect.
No differences were found in the number of correct answers
on Reality Questions at ANCOVA testing between paired
patients and healthy controls.

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S. Anselmetti et al. / Schizophrenia Research 115 (2009) 278285

Table 1
Demographic and clinical characteristics of the sample.
Offspring n = 47

Age
Education
Sex
Onset
Duration
TIB total
PANSS total
PANSS positive
PANSS negative
PANSS general

Fathers n = 47

Mothers n = 47

Patients

Controls

Patients

Controls

Patients

Controls

Mean SD

Mean SD

Mean SD

Mean SD

Mean SD

Mean SD

32.1 7.8
11.4 2.9
16 F 30 M
22.7 4.7
9.4 6.6
103.7 5.4
79.1 19.7
14.5 4.3
21.4 6.7
33.1 8.4

29.8 5.2
15.1 2.9
22 F 25 M

62.4 8.3
10.1 4.2

115.4 3.02

109.2 6.6

54.6 11.6
12.3 4.1

113 4.63

60.2 8.6
9.1 3.7

108.7 5.9

55.1 8.2
11.6 4.0

112.8 5.3

p = .000.
p < .01.
p < .05.

4.2.2. Parents of patients vs. parents of controls

4.2.2.1. Total Score. The ANCOVA group effect was signicant
(F = 4.07 p =.008) as well as the covariate effect of Symbol
Coding Task (F = 15.4 p = .000) (Table 3). Post-hoc analysis
showed signicantly worse performance on the part of patients'
mothers compared to controls' mothers and patients' fathers
compared to controls' fathers (p <.001 for all the comparisons).
4.2.2.2. Reaction Time Score. The ANCOVA group effect was
signicant (F = 14.43 p < .001) as well as the covariate effect
of Symbol Coding Task (F = 6.37 p < .001). At the post-hoc
analysis both patients' fathers and patients' mothers showed
signicantly worse performance than controls' fathers and
controls' mothers (p < .002 for all the comparisons).
No differences were found in the number of correct
answers on Reality Questions with ANCOVA testing between
paired parents of the two family groups.
No differences were found in ToM performance within the
parents of patients group regarding the presence/absence of a
familiar history of psychosis in parents' ancestors.
4.3. Predictors of overall Theory of mind performance
A regression analysis was carried out separately for
patients, their mothers and their fathers to further address
Table 2
Neuropsychological performance and performance on Picture Sequencing
Task of patients and controls.
Offspring
Patients

Controls

Statistic

Mean SD

Mean SD

ANCOVA

36.9 9.9

57.8 13.2

F = 59.01 p < .001

17.7 11.2

4.5 8.2

ToM Picture Sequencing Task

Total Score
33.7 10.3
Reality Questions (%)
88.1 21.1
Reaction Time (s)
46.8 17.8

50.8 4.3
98.9 7.3
25.4 9.4

BACS Symbol coding

task (n)
WCST (n perseverative
errors)

F = 19 p < .001

F = 15.2 p < .001

p = ns
F = 10.42 p = .002

the question of whether cognitive functioning could account

for impairment in ToM performance in families of patients
with schizophrenia. A multiple regression analysis was performed including age, education, Symbol Coding task, WCST
scores and Total IQ (TIB score) as continuous independent
variables and Total Score of the ToM Picture Sequencing Task
as dependent variable.
The analysis revealed a signicant overall model for
patients (R2 = .34 F = 4.93 p = .001) and showed that
patients' ToM performance was predicted by premorbid IQ
(F = 5.13 p = .02), Symbol Coding task performance (F = 4.9
p = .05) and number of WCST perseverative errors (F = 3.8
p = .04).
The model was not signicant for patients' mothers nor for
fathers.
5. Discussion
At our best knowledge, this is the rst study assessing ToM
functioning by focusing on parents of patients with schizophrenia, and not on the broader category of rst-degree
relatives. We tried to compare performance of whole trios of
control and patients' families while considering the possible
effect of the neuropsychological impairment, which is wellknown to affect rst-degree relatives of patients with
schizophrenia (Appels et al., 2003).
The choice to include parents only was determined by the
advantage of measuring social cognitive performance among
those relatives with the stronger potential to inuence the
future patient's performance (Docherty, 1994; Meins et al.,
2002) during early stages of development. The choice to carry
separate analysis was due to the hypothesis of a differential
role of mothers and fathers in the offspring development, as
previously argued in literature (Ruffman et al., 2002; Meins
et al., 2002).
Nevertheless literature suggests that rst-degree relatives,
including parents (Kremen et al., 1994; Appels et al., 2003),
show impaired neuropsychological performance compared
to controls, in the cognitive domains considered by part of
literature (Brune, 2005; Greig et al., 2004) as supporting ToM
impaired performance in schizophrenia. According to this view,
we rst analyzed ToM performance differences between

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283

Table 3
Neuropsychological performance and performance on Picture Sequencing Task of parents of patients and controls.
Fathers

Mothers

Patients

Controls

Patients

Controls

Statistic

Mean SD

Mean SD

Mean SD

Mean SD

ANCOVA

BACS Symbol coding task (n)

WCST (n perseverative errors)

42.4 13.0
15.5 11.7

50.9 11.3
9.6 9.0

40.3 13.0
16.5 10.8

52.5 10.5
9.3 6.0

F = 3.8 p = .01
p = ns

ToM Picture Sequencing Task

Total Score
Reality Questions (%)
Reaction Time (s)

46.7 8.3
93.5 17
41.1 21.7

52.1 8.6
96.8 12.3
28.4 13.3

43.9 9.8
89.7 25.9
48.3 27.6

51.7 9.6
97.9 17.1
28.9 13.7

F = 13.39 p < .001

p = ns
F = 8.5 p = .004

groups of subjects considering the two neuropsychological

functions that were more frequently related by literature to
ToM performance (executive function and sustained attention)
as covariates. Additionally, we quantitatively evaluated the
possible contribution of neuropsychological performance to
ToM performance within each group in a multivariate
regression model, in order to assess possible different models
depending on the status of relationship with schizophrenia
(patient, parent of patient, control and parent of control).
The neuropsychological functioning of parents of patients
with schizophrenia was impaired compared to the control group
in the Symbol Coding Task. This nding is consistent with previous reports showing cognitive decits of relatives of patients
with schizophrenia in selected neurocognitive domains, especially on attention and speed of information processing (Snitz
et al., 2006; Dickinson et al., 2007; Ma et al., 2007). Specically,
results on the Symbol Coding Task conrm previous studies on
rst-degree relatives using this paradigm (see Dickinson et al.,
2007, for a metanalysis). Different abilities are needed to
perform the task, including encoding and retrieval operations,
perceptual processes, use of information held in working
memory, and decision processes (Dickinson et al., 2007; Byrne
et al., 2003; Niendam et al., 2003). This simple measure has
shown a graded relationship with illness risk, severity, and
disability in schizophrenia and differentiated people with
schizophrenia from healthy controls, low- and high-risk
relatives of people with schizophrenia from healthy controls,
and unaffected relatives from probands with schizophrenia
(Dickinson et al., 2007; Niendam et al., 2003). In the few studies
available selectively regarding parents (Appels et al., 2003;
Docherty, 1994) this performance was not specically tested,
but measures of sustained attention and psychomotor speed
were signicantly worse among parents of patients in comparison to controls. The Appels et al. (2003) study is consistent with
our results on WCST performance among parents, not signicantly different from the control parents. This result is not
surprising as the impairment of executive function in rstdegree relatives of patients with schizophrenia is somewhat
controversial, being found by some studies (Franke et al., 1994;
Goldberg et al., 1990; Dollfus et al., 2002) and not found by
others (Laurent et al., 2002; Keefe et al., 1994) with differences
depending on the task used (Roxborough et al., 1993).
Regarding ToM performance, Picture Sequencing Task
results showed that non-psychotic parents of patients with
schizophrenia have worse ToM performance when compared
to healthy controls, even adjusting for cognitive functioning.
Despite the signicant covariate effects of Symbol Coding, the

difference in ToM performance between parents of patients

and parents of controls remained signicant, supporting
previous data on ToM (Janssen et al., 2003).
It is interesting that in the analysis comparing patients and
controls the covariate effects involved all of the neuropsychological measures we included, while only Symbol Coding
Task was a signicant covariate for the analysis comparing
parents of patients with parents of healthy controls. This discrepancy may suggest a difference in the cognitive context in
which the ToM impairment develops. Patients and their
parents were not signicantly impaired in answering Reality
Questions about the test vignettes, a set of control questions
involving only the general ability of physical information
processing rather than ToM. This last result is similar to that
of Brune (2003), supporting, on the same testing material, the
hypothesis of a specic ToM processing impairment in
schizophrenia instead of a generic impairment in processing
ability, and extending this hypothesis to parents of people with
schizophrenia.
Neuropsychological results from our study are supported
by recent fMRI research that demonstrated that ToM can be
dissociated from other cognitive functions and that performance is related to a relatively specialized social cognitive
network in the brain, including the medial prefrontal and
cingulate cortex (MPFC), the posterior cingulate cortex and
bilateral temporo-parietal regions (Gallagher and Frith, 2003;
Saxe, 2006; Ciaramidaro et al., 2007; Walter et al., 2009).
Our results are not consistent with those of the Kelemen
et al. (2004) study, where they failed to nd signicant
differences between healthy controls and rst-degree relatives
of schizophrenia in the Eyes Task, a measure of facial affect
recognition. This inconsistency is consistent with the hypothesis that within the social domain, patients' cognitive and
affective abilities may be affected independently (ShamayTsoory et al., 2007). Moreover the task we used is not intended
for affective ToM abilities like the Eyes Task and the participants
were requested to infer the mental states of characters by the
interpretation of complex verbal material.
Both patients and their parents were signicantly slower
than control families in sorting ToM picture stories, even
when controlling for cognitive functioning. This slowness on
the part of both patients and parents might be related to
impaired processing of the social interaction depicted in the
stories, as it may reect the processing demands of other
more complex supportive or compensatory strategies and not
only the effect of impaired executive function and attention
(Mazza et al., 2001; Brune, 2005).

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S. Anselmetti et al. / Schizophrenia Research 115 (2009) 278285

Among patients, the multiple regression model was statistically signicant and showed that the signicant predictors
of the ToM performance were Symbol Coding Task performance, WCST performance and premorbid IQ. This result was
expected, due to the signicant demands of the ToM tasks on
attention, psychomotor speed and executive function (Mazza
et al., 2001; Brune, 2005). Also the signicant inuence of
premorbid IQ on the ToM performance is consistent with
previous studies showing a role of IQ in the ability to recognize
mental states (Brune, 2005; Mazza et al., 2001). On the other
hand we did not nd any signicant predictors for parents of
patients, as if their impaired ToM performance was not
quantitatively related to their neuropsychological performances, but rather a parallel trait.
These results altogether suggest that impairment in Symbol
Coding Task and ToM Picture Sequencing Task performance are
traits present both in patients and their parents, but that they
are not strictly correlated in determining ToM performance in
the absence of illness. However, the full phenotypical expression of the illness in the patients could be critical in explaining
the different relationships between ToM and cognitive functions in general. These results raise the question if other
functions compensate for the ToM decit in parents of patients.
This question leads to a limitation of our study, as we explored
neuropsychological abilities suggested by literature as possibly
related to ToM and not a complete panel of cognitive functions
related to the illness.
The present study has other limitations. First, trios of
healthy and patients' families were different in age and education. These factors are known to strongly affect cognition
and ToM performance. This problem was reduced covarying
out their effect in the analysis of variance, but we could not
exclude that lower education could explain a proportion of
variance in ToM impairments both in parents of patients and
in their offspring. Second, we excluded trios with at least one
parent with a history of psychotic illness to ensure that
cognitive performance in parents was not directly related to a
fully expressed clinical condition and that this might have
limited the role of a heavy genetic load for illness. Moreover, we did not include any measurements of functional
consequences in parents of patients. This topic should be
addressed in future studies, trying to answer the question if
ToM impairments also in parents of patients with schizophrenia could affect their social ability in real life.
In conclusion, the ndings of the present study provide
some descriptive information about impairment in recognizing
mental states of others present in parents of patients. However,
our results cannot answer questions about the aetiological
relevance of the impairment in families. Further larger studies
are needed to address this question, in particular genetic
studies with plausible future candidate genes, but also studies
aimed at exploring other hypotheses on family patterns of
social cognition performance.
Role of funding source
This study has no funding source.
Contributors
Simona Anselmetti and Roberto Cavallaro designed the study and wrote
the research protocol. Camilla Quarticelli, Margherita Bechi and Elena Ermoli
administered the neuropsychological tests to the participants. Marta Bosia
and Simona Anselmetti undertook the statistical analysis, and Simona

Anselmetti wrote the rst draft of the manuscript. Enrico Smeraldi was the
last reader of the paper and gave suggestions for the improvement of the
text. All authors contributed to and have approved the nal manuscript.
Conict of interest
All authors declare that they have no conicts of interest.
Acknowledgement
There are no acknowledgement.

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